Intermedin Alleviates Renal Ischemia-Reperfusion Injury and Enhances Neovascularization in Wistar Rats

Yanhong Wang,1,* Yang Mi,2,* Jihua Tian,1,* Xi Qiao,3 Xiaole Su,3 Jing Kang,1 Zhijing Wu,1 Guiqing Wang,1 Xiaoshuang Zhou,4 Yun Zhou,4 Rongshan Li4 1Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Urology, Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun ZhouDepartment of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, No. 29 Shuang Ta East Street, Taiyuan, Shanxi 030012, People’s Republic of ChinaEmail zhouyun_sx@163.comRongshan LiDepartment of Nephrology, The Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, No. 29 Shuang Ta East Street, Taiyuan 030012, People’s Republic of ChinaEmail rongshanli13@163.comBackground: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and increases the risk of subsequently developing chronic kidney disease. Angiogenesis has been shown to play an important role in reducing renal injury after ischemia reperfusion. In this study, we investigated whether IMD could reduce renal IRI by promoting angiogenesis.Methods: The kidneys of Wistar rats were subjected to 45 min of warm ischemia followed by 24 h of reperfusion. IMD was overexpressed in vivo using the vector pcDNA3.1-IMD transfected by an ultrasound-mediated system. The renal injury after ischemia reperfusion was assessed by detection of the serum creatinine concentration and histologic examinations of renal tissues stained by PAS and H&E. Real-time PCR and Western blotting were used to determine the mRNA and protein levels, respectively. Histological examinations were used to assess the expression of CD31, MMP2, MMP9, ET-1, VEGF and VEGFR2 in tissues.Results: Renal function and renal histological damage were significantly ameliorated in IMD-transfected rats after ischemia reperfusion. Compared to the IRI, IMD significantly promoted angiogenesis. IMD also upregulated the protein and mRNA expression levels of VEGF and VEGFR2 and downregulated the expression level of MMP2, MMP9 and ET-1.Conclusion: IMD could protect the kidney after renal ischemia-reperfusion injury by promoting angiogenesis and reducing the destruction of the perivascular matrix.Keywords: intermedin, ischemia-reperfusion injury, kidney, angiogenesis, VEGF, VEGFR2, MMP2, MMP9, ET-1